MNDO research on alkylation of DNA bases by the non-α-position metabolite of 3,5-dimethyl-N-nitrosopeperazine

摘要

IT is a commonly accepted concept that having formed alkyldiazonium ions after α-hydroxyla-tion, the metabolites of N-nitroso compounds (NNCs) combine with DNA and initiate cancer. But the complex relationship between carcinogenicities of NNCs and their molecular structure cannot be well explained by their α-position activities . More and more experimental evidence shows that the metabolism of non-α-position of NNC molecules plays a considerable role in car-cinogenesis . By pattern recognition, westudied the quantitative relationship between 153 NNCs' structures and their carcinogenicities, and the results show that the essential condition for NNC molecule to be an ultimate carcinogen is to form two active electrophilic positions in one NNC molecule through metabolism or spontaneous decomposition. And the most suitable distance between the two active positions is about 280 pm.